tbuckley/cabot-search huggingface dataset:
Erratum. 4. Comprehensive Medical Evaluation and Assessment of Comorbidities: <i>Standards of Care in Diabetes—2023</i>. Diabetes Care 2023;46(Suppl. 1):S49–S67
Authors: Nuha A. ElSayed, Grazia Aleppo, Vanita R. Aroda, Raveendhara R. Bannuru, Florence M. Brown, Dennis Bruemmer, Billy S. Collins, Kenneth Cusi, Marisa E. Hilliard, Diana Isaacs, Eric L. Johnson, Scott Kahan, Kamlesh Khunti, Jose Leon, Sarah K. Lyons, Mary Lou Perry, Priya Prahalad, Richard E. Pratley, Jane Jeffrie Seley, Robert C. Stanton, Robert A. Gabbay
Journal: Diabetes Care (2023)

In the section “Assessment of Comorbidities” of the article cited above, the subsections “Hepatitis C Infection,” “Pancreatitis,” “Fractures,” “Sensory Impairment,” and “Low Testosterone in Men,” present in the 2022 guidelines, were inadvertently omitted.
Effect of the P-Selectin Inhibitor Crizanlizumab on Survival Free of Organ Support in Patients Hospitalized for COVID-19: A Randomized Controlled Trial
Authors: Scott D. Solomon, Charles J. Lowenstein, Ankeet S. Bhatt, Alexander Peikert, Orly Vardeny, Mikhail N. Kosiborod, Jeffrey S. Berger, Harmony R. Reynolds, Stephanie Mavromichalis, Anya Barytol, Andrew D. Althouse, James F. Luther, Eric S. Leifer, Andrei L. Kindzelski, Mary Cushman, Michelle N. Gong, Lucy Z. Kornblith, Pooja Khatri, Keri S. Kim, Lisa Baumann Kreuziger, Lana Wahid, Bridget-Anne Kirwan, Mark W. Geraci, Matthew D. Neal, Judith S. Hochman
Journal: Circulation (2023)

BACKGROUND: COVID-19 has been associated with endothelial injury, resultant microvascular inflammation and thrombosis. Activated endothelial cells release and express P-selectin and von Willebrand factor, both of which are elevated in severe COVID-19 and may be implicated in the disease pathophysiology. We hypothesized that crizanlizumab, a humanized monoclonal antibody to P-selectin, would reduce morbidity and death in patients hospitalized for COVID-19. METHODS: An international, adaptive, randomized controlled platform trial, funded by the National Heart, Lung, and Blood Institute, randomly assigned 422 patients hospitalized with COVID-19 with moderate or severe illness to receive either a single infusion of the P-selectin inhibitor crizanlizumab (at a dose of 5 mg/kg) plus standard of care or standard of care alone in an open-label 1:1 ratio. The primary outcome was organ support–free days, evaluated on an ordinal scale consisting of the number of days alive free of organ support through the first 21 days after trial entry. RESULTS: The study was stopped for futility by the data safety monitoring committee. Among 421 randomized patients with known 21-day outcomes, 163 patients (77%) randomized to the crizanlizumab plus standard-of-care arm did not require any respiratory or cardiovascular organ support compared with 169 (80%) in the standard-of-care–alone arm. The adjusted odds ratio for the effect of crizanlizumab on organ support–free days was 0.70 (95% CI, 0.43–1.16), where an odds ratio &gt;1 indicates treatment benefit, yielding a posterior probability of futility (odds ratio &lt;1.2) of 98% and a posterior probability of inferiority (odds ratio &lt;1.0) of 91%. Overall, there were 37 deaths (17.5%) in the crizanlizumab arm and 27 deaths (12.8%) in the standard-of-care arm (hazard ratio, 1.33 [95% CrI, 0.85-2.21]; [probability of hazard ratio&gt;1] = 0.879). CONCLUSIONS: Crizanlizumab, a P-selectin inhibitor, did not result in improvement in organ support–free days in patients hospitalized with COVID-19. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04505774.
Addendum. 4. Comprehensive Medical Evaluation and Assessment of Comorbidities: <i>Standards of Care in Diabetes—2023</i>. Diabetes Care 2023;46(Suppl. 1):S49–S67
Authors: Nuha A. ElSayed, Grazia Aleppo, Vanita R. Aroda, Raveendhara R. Bannuru, Florence M. Brown, Dennis Bruemmer, Billy S. Collins, Kenneth Cusi, Marisa E. Hilliard, Diana Isaacs, Eric L. Johnson, Scott Kahan, Kamlesh Khunti, Jose Leon, Sarah K. Lyons, Mary Lou Perry, Priya Prahalad, Richard E. Pratley, Jane Jeffrie Seley, Robert C. Stanton, Robert A. Gabbay
Journal: Diabetes Care (2023)

Section 4, “Comprehensive Medical Evaluation and Assessment of Comorbidities,” of the Standards of Care in Diabetes—2023 has been updated to reflect the current clinical knowledge and evidence in nonalcoholic fatty liver disease (NAFLD).
Phosphomevalonate kinase deficiency expands the genetic spectrum of systemic autoinflammatory diseases
Authors: Jakob Berner, Cheryl van de Wetering, Raul Jimenez Heredia, Christina Rashkova, Sacha Ferdinandusse, Janet Koster, Johannes G. Weiss, Alexandra Frohne, Sarah Giuliani, Hans R. Waterham, Irinka Castanon, Jürgen Brunner, Kaan Boztug
Journal: Journal of Allergy and Clinical Immunology (2023)

In the isoprenoid biosynthesis pathway, mevalonate is phosphorylated in 2 subsequent enzyme steps by MVK and PMVK to generate mevalonate pyrophosphate that is further metabolized to produce sterol and nonsterol isoprenoids. Biallelic pathogenic variants in MVK result in the autoinflammatory metabolic disorder MVK deficiency. So far, however, no patients with proven PMVK deficiency due to biallelic pathogenic variants in PMVK have been reported.This study reports the first patient with functionally confirmed PMVK deficiency, including the clinical, biochemical, and immunological consequences of a homozygous missense variant in PMVK.The investigators performed whole-exome sequencing and functional studies in cells from a patient who, on clinical and immunological evaluation, was suspected of an autoinflammatory disease.The investigators identified a homozygous PMVK p.Val131Ala (NM_006556.4: c.392T>C) missense variant in the index patient. Pathogenicity was supported by genetic algorithms and modeling analysis and confirmed in patient cells that revealed markedly reduced PMVK enzyme activity due to a virtually complete absence of PMVK protein. Clinically, the patient showed various similarities as well as distinct features compared to patients with MVK deficiency and responded well to therapeutic IL-1 inhibition.This study reported the first patient with proven PMVK deficiency due to a homozygous missense variant in PMVK, leading to an autoinflammatory disease. PMVK deficiency expands the genetic spectrum of systemic autoinflammatory diseases, characterized by recurrent fevers, arthritis, and cytopenia and thus should be included in the differential diagnosis and genetic testing for systemic autoinflammatory diseases.
Tumor Microenvironment Landscape of NSCLC Reveals Resistance Mechanisms for Programmed Death-Ligand 1 Blockade After Chemoradiotherapy: A Multicenter Prospective Biomarker Study (WJOG11518L:SUBMARINE)
Authors: Koji Haratani, Atsushi Nakamura, Nobuaki Mamesaya, Shigeki Mitsuoka, Yasuto Yoneshima, Ryota Saito, Junko Tanizaki, Yasuhito Fujisaka, Akito Hata, Kosuke Tsuruno, Tomohiro Sakamoto, Shunsuke Teraoka, Masahide Oki, Hiroshi Watanabe, Yuki Sato, Yusuke Nakano, Tomoyuki Otani, Kazuko Sakai, Shuta Tomida, Yasutaka Chiba, Akihiko Ito, Kazuto Nishio, Nobuyuki Yamamoto, Kazuhiko Nakagawa, Hidetoshi Hayashi
Journal: Journal of Thoracic Oncology (2023)
Cystatin C is glucocorticoid responsive, directs recruitment of Trem2+ macrophages, and predicts failure of cancer immunotherapy
Authors: Sam O. Kleeman, Tuba Mansoor Thakir, Breanna Demestichas, Nicholas Mourikis, Dominik Loiero, Miriam Ferrer, Sean Bankier, Yosef J.R.A. Riazat-Kesh, Hassal Lee, Dimitrios Chantzichristos, Claire Regan, Jonathan Preall, Sarthak Sinha, Nicole Rosin, Bryan Yipp, Luiz G.N. de Almeida, Jeff Biernaskie, Antoine Dufour, Pinkus Tober-Lau, Arno Ruusalepp, Johan L.M. Bjorkegren, Markus Ralser, Florian Kurth, Vadim Demichev, Todd Heywood, Qing Gao, Gudmundur Johannsson, Viktor H. Koelzer, Brian R. Walker, Hannah V. Meyer, Tobias Janowitz
Journal: Cell Genomics (2023)

Cystatin C (CyC), a secreted cysteine protease inhibitor, has unclear biological functions. Many patients exhibit elevated plasma CyC levels, particularly during glucocorticoid (GC) treatment. This study links GCs with CyC's systemic regulation by utilizing genome-wide association and structural equation modeling to determine CyC production genetics in the UK Biobank. Both CyC production and a polygenic score (PGS) capturing predisposition to CyC production were associated with increased all-cause and cancer-specific mortality. We found that the GC receptor directly targets CyC, leading to GC-responsive CyC secretion in macrophages and cancer cells. CyC-knockout tumors displayed significantly reduced growth and diminished recruitment of TREM2+ macrophages, which have been connected to cancer immunotherapy failure. Furthermore, the CyC-production PGS predicted checkpoint immunotherapy failure in 685 patients with metastatic cancer from combined clinical trial cohorts. In conclusion, CyC may act as a GC effector pathway via TREM2+ macrophage recruitment and may be a potential target for combination cancer immunotherapy.
Accurate microRNA annotation of animal genomes using trained covariance models of curated microRNA complements in MirMachine
Authors: Sinan Uğur Umu, Vanessa M. Paynter, Håvard Trondsen, Tilo Buschmann, Trine B. Rounge, Kevin J. Peterson, Bastian Fromm
Journal: Cell Genomics (2023)

The annotation of microRNAs depends on the availability of transcriptomics data and expert knowledge. This has led to a gap between the availability of novel genomes and high-quality microRNA complements. Using >16,000 microRNAs from the manually curated microRNA gene database MirGeneDB, we generated trained covariance models for all conserved microRNA families. These models are available in our tool MirMachine, which annotates conserved microRNAs within genomes. We successfully applied MirMachine to a range of animal species, including those with large genomes and genome duplications and extinct species, where small RNA sequencing is hard to achieve. We further describe a microRNA score of expected microRNAs that can be used to assess the completeness of genome assemblies. MirMachine closes a long-persisting gap in the microRNA field by facilitating automated genome annotation pipelines and deeper studies into the evolution of genome regulation, even in extinct organisms.
Post COVID-19 condition, work ability and occupational changes in a population-based cohort
Authors: Philipp Kerksieck, Tala Ballouz, Sarah R. Haile, Celine Schumacher, Joanne Lacy, Anja Domenghino, Jan S. Fehr, Georg F. Bauer, Holger Dressel, Milo A. Puhan, Dominik Menges
Journal: The Lancet Regional Health - Europe (2023)

Evidence on the impact of post COVID-19 condition (PCC) on work ability is limited but critical due to its high prevalence among working-age individuals. This study aimed to evaluate the association between PCC, work ability, and occupational changes in a population-based cohort.We used data from working-age adults included in a prospective, longitudinal cohort of a random sample of all individuals infected with SARS-CoV-2 between August 2020 and January 2021 in the Canton of Zurich, Switzerland. We evaluated current work ability, work ability related to physical and mental demands, and estimated future work ability in 2 years (assessed using Work Ability Index), and PCC-related occupational changes one year after infection.Of 672 individuals included in this study, 120 (17.9%) were categorised as having PCC (defined as presence of self-reported COVID-19 related symptoms) at 12 months. There was very strong evidence that current work ability scores were mean 0.62 (95% CI 0.30-0.95) points lower among those with PCC compared to those without in adjusted regression analyses. Similarly, there was very strong evidence for lower odds of reporting higher work ability with respect to physical (adjusted odds ratio (aOR) 0.30, 95% CI 0.20-0.46) and mental (aOR 0.40, 0.27-0.62) demands in individuals with PCC. Higher age and history of psychiatric diagnosis were associated with more substantial reductions in current work ability. 5.8% of those with PCC reported direct effects of PCC on their occupational situation, with 1.6% of those with PCC completely dropping out of the workforce.These findings highlight the need for providing support and interdisciplinary interventions to individuals affected by PCC to help them maintain or regain their work ability and productivity.Federal Office of Public Health, Department of Health of the Canton of Zurich, University of Zurich Foundation, Switzerland; Horizon Europe.
Faecal carriage of extended-spectrum β-lactamase-producing Escherichia coli in a remote region of Niger
Authors: Hervé Jacquier, Bachir Assao, Françoise Chau, Ousmane Guindo, Bénédicte Condamine, Mélanie Magnan, Antoine Bridier-Nahmias, Nathan Sayingoza-Makombe, Aissatou Moumouni, Anne-Laure Page, Céline Langendorf, Matthew E. Coldiron, Erick Denamur, Victoire de Lastours
Journal: Journal of Infection (2023)
Efficacy and safety of once-daily oral semaglutide 25 mg and 50 mg compared with 14 mg in adults with type 2 diabetes (PIONEER PLUS): a multicentre, randomised, phase 3b trial
Authors: Vanita R Aroda, Jens Aberle, Lars Bardtrum, Erik Christiansen, Filip K Knop, Sanaz Gabery, Sue D Pedersen, John B Buse
Journal: The Lancet (2023)
Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial
Authors: Filip K Knop, Vanita R Aroda, Ruben D do Vale, Thomas Holst-Hansen, Peter N Laursen, Julio Rosenstock, Domenica M Rubino, W Timothy Garvey
Journal: The Lancet (2023)
Blood cell traits’ GWAS loci colocalization with variation in PU.1 genomic occupancy prioritizes causal noncoding regulatory variants
Authors: Raehoon Jeong, Martha L. Bulyk
Journal: Cell Genomics (2023)

Genome-wide association studies (GWASs) have uncovered numerous trait-associated loci across the human genome, most of which are located in noncoding regions, making interpretation difficult. Moreover, causal variants are hard to statistically fine-map at many loci because of widespread linkage disequilibrium. To address this challenge, we present a strategy utilizing transcription factor (TF) binding quantitative trait loci (bQTLs) for colocalization analysis to identify trait associations likely mediated by TF occupancy variation and to pinpoint likely causal variants using motif scores. We applied this approach to PU.1 bQTLs in lymphoblastoid cell lines and blood cell trait GWAS data. Colocalization analysis revealed 69 blood cell trait GWAS loci putatively driven by PU.1 occupancy variation. We nominate PU.1 motif-altering variants as the likely shared causal variants at 51 loci. Such integration of TF bQTL data with other GWAS data may reveal transcriptional regulatory mechanisms and causal noncoding variants underlying additional complex traits.
A bio-instructive parylene-based conformal coating suppresses thrombosis and intimal hyperplasia of implantable vascular devices
Authors: Dake Hao, Jonathan Lin, Ruiwu Liu, Christopher Pivetti, Kaeli Yamashiro, Linda M. Schutzman, Junichiro Sageshima, Mimmie Kwong, Nataliya Bahatyrevich, Diana L. Farmer, Misty D. Humphries, Kit S. Lam, Alyssa Panitch, Aijun Wang
Journal: Bioactive Materials (2023)

Implantable vascular devices are widely used in clinical treatments for various vascular diseases. However, current approved clinical implantable vascular devices generally have high failure rates primarily due to their surface lacking inherent functional endothelium. Here, inspired by the pathological mechanisms of vascular device failure and physiological functions of native endothelium, we developed a new generation of bioactive parylene (poly(p-xylylene))-based conformal coating to address these challenges of the vascular devices. This coating used a polyethylene glycol (PEG) linker to introduce an endothelial progenitor cell (EPC) specific binding ligand LXW7 (cGRGDdvc) onto the vascular devices for preventing platelet adhesion and selectively capturing endogenous EPCs. Also, we confirmed the long-term stability and function of this coating in human serum. Using two vascular disease-related large animal models, a porcine carotid artery interposition model and a porcine carotid artery-jugular vein arteriovenous graft model, we demonstrated that this coating enabled rapid generation of self-renewable "living" endothelium on the blood contacting surface of the expanded polytetrafluoroethylene (ePTFE) grafts after implantation. We expect this easy-to-apply conformal coating will present a promising avenue to engineer surface properties of "off-the-shelf" implantable vascular devices for long-lasting performance in the clinical settings.
An ischemic area-targeting, peroxynitrite-responsive, biomimetic carbon monoxide nanogenerator for preventing myocardial ischemia-reperfusion injury
Authors: Jinyan Zhang, Liwei Liu, Zhen Dong, Xicun Lu, Wenxuan Hong, Jin Liu, Xiaoyi Zou, Jinfeng Gao, Hao Jiang, Xiaolei Sun, Kai Hu, Youjun Yang, Junbo Ge, Xiao Luo, Aijun Sun
Journal: Bioactive Materials (2023)

Myocardial ischemia-reperfusion (MI/R) injury is common in patients who undergo revascularization therapy for myocardial infarction, often leading to cardiac dysfunction. Carbon monoxide (CO) has emerged as a therapeutic molecule due to its beneficial properties such as anti-inflammatory, anti-apoptotic, and mitochondrial biogenesis-promoting properties. However, its clinical application is limited due to uncontrolled release, potential toxicity, and poor targeting efficiency. To address these limitations, a peroxynitrite (ONOO-)-triggered CO donor (PCOD585) is utilized to generate a poly (lactic-co-glycolic acid) (PLGA)-based, biomimetic CO nanogenerator (M/PCOD@PLGA) that is coated with the macrophage membrane, which could target to the ischemic area and neutralize proinflammatory cytokines. In the ischemic area, local produced ONOO- triggers the continuous release of CO from M/PCOD@PLGA, which efficiently ameliorates MI/R injury by clearing harmful ONOO-, attenuating the inflammatory response, inhibiting cardiomyocyte apoptosis, and promoting mitochondrial biogenesis. This study provides a novel insight into the safe therapeutic use of CO for MI/R injury by utilizing a novel CO donor combined with biomimetic technology. The M/PCOD@PLGA nanogenerator offers targeted delivery of CO to the ischemic area, minimizing potential toxicity and enhancing therapeutic efficacy.
Current concepts, advances, and challenges in deciphering the human microbiota with metatranscriptomics
Authors: Teija Ojala, Aino-Elina Häkkinen, Esko Kankuri, Matti Kankainen
Journal: Trends in Genetics (2023)

Metatranscriptomics refers to the analysis of the collective microbial transcriptome of a sample. Its increased utilization for the characterization of human-associated microbial communities has enabled the discovery of many disease-state related microbial activities. Here, we review the principles of metatranscriptomics-based analysis of human-associated microbial samples. We describe strengths and weaknesses of popular sample preparation, sequencing, and bioinformatics approaches and summarize strategies for their use. We then discuss how human-associated microbial communities have recently been examined and how their characterization may change. We conclude that metatranscriptomics insights into human microbiotas under health and disease have not only expanded our knowledge on human health, but also opened avenues for rational antimicrobial drug use and disease management.
Biophilia revisited: nature versus nurture
Authors: Bengt Gunnarsson, Marcus Hedblom
Journal: Trends in Ecology & Evolution (2023)

The 'Biophilia' hypothesis highlighting humans' innate, positive response to nature is both increasingly accepted and questioned. Studies support an updated Biophilia. The interplay between inheritance and environment, including culture, governs an individual's response, from positive to negative. Variety in urban green spaces is needed to optimise benefits to all residents.
What benefit can be obtained from magnetic resonance imaging diagnosis with artificial intelligence in prostate cancer compared with clinical assessments?
Authors: Li-Tao Zhao, Zhen-Yu Liu, Wan-Fang Xie, Li-Zhi Shao, Jian Lu, Jie Tian, Jian-Gang Liu
Journal: Military Medical Research (2023)

Abstract The present study aimed to explore the potential of artificial intelligence (AI) methodology based on magnetic resonance (MR) images to aid in the management of prostate cancer (PCa). To this end, we reviewed and summarized the studies comparing the diagnostic and predictive performance for PCa between AI and common clinical assessment methods based on MR images and/or clinical characteristics, thereby investigating whether AI methods are generally superior to common clinical assessment methods for the diagnosis and prediction fields of PCa. First, we found that, in the included studies of the present study, AI methods were generally equal to or better than the clinical assessment methods for the risk assessment of PCa, such as risk stratification of prostate lesions and the prediction of therapeutic outcomes or PCa progression. In particular, for the diagnosis of clinically significant PCa, the AI methods achieved a higher summary receiver operator characteristic curve (SROC-AUC) than that of the clinical assessment methods (0.87 vs. 0.82). For the prediction of adverse pathology, the AI methods also achieved a higher SROC-AUC than that of the clinical assessment methods (0.86 vs. 0.75). Second, as revealed by the radiomics quality score (RQS), the studies included in the present study presented a relatively high total average RQS of 15.2 (11.0–20.0). Further, the scores of the individual RQS elements implied that the AI models in these studies were constructed with relatively perfect and standard radiomics processes, but the exact generalizability and clinical practicality of the AI models should be further validated using higher levels of evidence, such as prospective studies and open-testing datasets.
Efficacy and safety of microencapsulated benzoyl peroxide and microencapsulated tretinoin for the treatment of acne vulgaris: Results from two phase 3 double-blind, randomized, vehicle-controlled studies
Authors: James Del Rosso, Jeffrey Sugarman, Lawrence Green, Theodore Lain, Ofra Levy-Hacham, Rinat Mizrahi, Linda Stein Gold
Journal: Journal of the American Academy of Dermatology (2023)
Emerging Epigenetic and Posttranslational Mechanisms Controlling Resistance to Glucocorticoids in Acute Lymphoblastic Leukemia
Authors: Cristina Borin, Tim Pieters, Valentina Serafin, Panagiotis Ntziachristos
Journal: HemaSphere (2023)

Glucocorticoids are extensively used for the treatment of acute lymphoblastic leukemia as they pressure cancer cells to undergo apoptosis. Nevertheless, glucocorticoid partners, modifications, and mechanisms of action are hitherto poorly characterized. This hampers our understanding of therapy resistance, frequently occurring in leukemia despite the current therapeutic combinations using glucocorticoids in acute lymphoblastic leukemia. In this review, we initially cover the traditional view of glucocorticoid resistance and ways of targeting this resistance. We discuss recent progress in our understanding of chromatin and posttranslational properties of the glucocorticoid receptor that might be proven beneficial in our efforts to understand and target therapy resistance. We discuss emerging roles of pathways and proteins such as the lymphocyte-specific kinase that antagonizes glucocorticoid receptor activation and nuclear translocation. In addition, we provide an overview of ongoing therapeutic approaches that sensitize cells to glucocorticoids including small molecule inhibitors and proteolysis-targeting chimeras.